Frank D. Morrow

Clinical and Metabolic Efficacy of Glutamine-supplemented Parenteral Nutrition after Bone Marrow Transplantation: A Randomized, Double-Blind, Controlled Study

OBJECTIVE To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation. DESIGN Double-blind, randomized, controlled clinical trial. SETTING University teaching hospital. PATIENTS Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies. INTERVENTION Parenteral nutrition was initiated the day after bone marrow transplantation (day 1). The experimental solution was supplemented with L-glutamine (0.57 g/kg body weight per day) and provided estimated requirements for energy and protein. The control solution was a standard, glutamine-free, isonitrogenous, isocaloric formula. MEASUREMENTS Nitrogen balance was determined between days 4 and 11 in the initial 23 patients. The incidence of clinical infection and microbial colonization, time until bone marrow engraftment, indices of clinical care, and other data related to hospital morbidity were recorded for all patients. RESULTS The glutamine-supplemented patients (n = 24) were clinically similar to the controls (n = 21) at entry. Nutrient intake was similar in both groups; however, nitrogen balance was improved in the glutamine-supplemented patients relative to the controls (-1.4 +/- 0.5 g/d compared with -4.2 +/- 1.2; P = 0.002). Fewer experimental patients developed clinical infection (three compared with nine in the control group; P = 0.041), and the incidence of microbial colonization was also significantly reduced. Hospital stay was shortened in patients receiving glutamine supplementation (29 +/- 1 d compared with 36 +/- 2 d; P = 0.017). CONCLUSION Patients receiving glutamine-supplemented parenteral nutrition after bone marrow transplantation had improved nitrogen balance, a diminished incidence of clinical infection, lower rates of microbial colonization, and shortened hospital stay compared with patients receiving standard parenteral nutrition. These effects occurred despite no differences between groups in the incidence of fever, antibiotic requirements, or time to neutrophil engraftment.

Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis

The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria.

Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people.

Depression among elderly people with reversible cognitive loss often manifests with concomitant vascular disease and can also precede the development of nonvascular degenerative dementia. Little is known about etiological factors for reversible or irreversible dementias in older depressed people. The amino acid homocysteine (HC), which is both a vascular disease risk factor and a precursor of the excitotoxic amino acids cysteine and homocysteic acid, could play a role in the pathophysiology of such individuals. Twenty‐seven depressed elderly acute inpatients by DSM‐III‐R criteria had significantly higher plasma homocysteine levels and lower cognitive screening test scores than did 15 depressed young adult inpatients. HC was highest in the older patients who had concomitant vascular diseases (n= 14). HC was lowest in the older depressives who had neither vascular illnesses nor dementia (n= 8), comparable to the young adult depressives. Higher HC correlated significantly with poorer cognition only in the nonvascular geriatric patients (rs= ‐0.53). The findings extend earlier work showing higher HC in vascular patients from general medical populations, and also suggest a possible metabolic factor in certain dementias associated with late‐life depression.

Relationship in humans between ascorbic acid consumption and levels of total and reduced ascorbic acid in lens, aqueous humor, and plasma.

The relationships between plasma, aqueous humor and lens ascorbic acid levels are examined in 131 samples from 127 patients. Mean ascorbate intake for nonsupplemented individuals was 148 mg/day or over two times the recommended daily allowance. A subset of 44 patients participated in a trial to assess the impact of vitamin C supplementation of 2 grams per day on aqueous and lens ascorbic acid levels. Such supplementation significantly increased both total and reduced ascorbic acid levels in plasma and aqueous and total ascorbic acid in the lens. Correlation coefficients relating total and reduced ascorbic acid levels in the three tissues ranged from 0.42 to 0.19 (p less than 0.05 for all correlation coefficients). Over 60% of the ascorbate was present in the reduced form in plasma and aqueous, and about 50% of the lens ascorbate was in the reduced form.

Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer

The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.

B Complex Vitamin Patterns in Geriatric and Young Adult Inpatients with Major Depression

This study compared the B complex vitamin status at time of admission of 20 geriatric and 16 young adult non‐alcoholic inpatients with major depression. Twenty‐eight percent of all subjects were deficient in B2 (riboflavin), B6 (pyridoxine), and/or B12 (cobalamin), but none in B1 (thiamine) or folate. The geriatric sample had significantly higher serum folate levels. Psychotic depressives had lower B12 than did non‐psychotic depressives. Poorer blood vitamin status was not associated with higher scores on the Hamilton Depression Rating Scale or lower scores on the Mini‐Mental State Examination in either age group. The data support the hypothesis that poorer status in certain B vitamins is present in major depression, but blood measures may not reflect central nervous system vitamin function or severity of affective syndromes as measured by the assays and scales in the present study.

Vascular disease risk factors, urinary free cortisol, and health histories in older adults: Shyness and gender interactions

We studied relationships between shyness and health during a health screening survey of older adults (ages 50-88) living in an active retirement community in the southwestern United States (n = 232). As in previous studies of infants, older individuals with hay fever, insomnia and constipation were more shy than those without these problems. Shy persons overall showed higher sitting systolic blood pressure and a larger fall in orthostatic systolic blood pressure on standing; shy men had a greater prevalence of hypertension histories than did low-shy men. Shy subjects of both sexes had lower HDL cholesterol and higher triglycerides than did low-shy subjects; shy women tended to have higher LDL cholesterol than did low-shy women. In contrast with findings of elevated salivary cortisol in extremely inhibited children of both sexes, only shy women had higher 24 h urinary free cortisol excretion than did low-shy women; men showed the opposite pattern, possibly related to suppression of aggression. Shy men also tended to report a higher prevalence of thyroid disease history than did low-shy men (20% versus 6%). Notably, autoimmune thyroiditis has previously been linked with panic and depression, disorders which in turn have been associated with shyness. Taken together with previous work in shy children and their families, the data raise the possibility of (a) increased risk for arteriosclerotic vascular disease; and (b) increased risk of adrenal- and/or thyroid-related diseases in certain shy older adults.

Reduced and total ascorbate in guinea pig eye tissues in response to dietary intake.

Guinea pigs were fed 5 different levels of dietary ascorbate representing a 65-fold range (0.8-52 mg animal-1 day-1). After two months on the diets, levels of reduced and total ascorbate were determined in aqueous humor, vitreous humor, lens and plasma. At low-dietary levels, proportionally higher levels of ascorbate are found in the lens than in other eye tissues. Tissue ascorbate levels began to plateau at dietary intake of approximately 11 mg animal-1 day-1. This is the amount suggested for optimal health, but it is ten times the level needed to prevent scurvy. Over 75% of the eye tissue ascorbate is in the reduced form in animals fed diets which provided 11 mg ascorbate. However, there was less than 50% reduced ascorbate in the eye tissues of the animals fed about 1mg ascorbate per day.

Test-Retest Reproducibility of the Relative Dose Response for Vitamin A Status in Guatemalan Adults: Issues of Diagnostic Sensitivity

The relative dose response (RDR) test has been used as a functional measure of whole-body stores of vitamin A in humans. We have examined the reproducibility of the RDR procedure in a population of Guatemalan adult subjects who would be expected to show a moderate prevalence of hypovitaminosis A. Fifty-one subjects were administered a standard RDR test, and the plasma samples were analyzed for retinol, tocopherol, retinol binding protein (RBP) and prealbumin (PAL). Thirty-four of the subjects underwent repeat RDR tests 7 d later. Plasma levels in fasted subjects were as follows: retinol, 1.35 +/- 0.30 mumol/L; RBP, 37.8 +/- 7.7 mg/L; PAL, 187.0 +/- 39.0 mg/L; and tocopherol, 16.6 +/- 6.2 mumol/L. RDRs ranged from -35.2% to +63.1%, with a mean of 2.6 +/- 10.4%. Overall, we observed poor within-subject reproducibility of the RDR procedure whether expressed numerically or by diagnostic classification. Moreover, in contrast to previous studies in children, we observed fewer positive RDR tests than would be expected for the population studied. Nevertheless, the mean RDR was inversely proportional to fasting retinol levels, thus confirming the validity of the biological basis of the RDR procedure in humans. Because of high intra-individual variability with this test, investigators should be cautious when using the RDR procedure in serial studies to monitor the efficacy of therapeutic interventions or subject compliance to dietary regimens.

The effect of fish oil supplementation on plasma α-tocopherol, retionol, lipid and lipoprotein levels in normolipidemic subjects

Abstract The effects of supplementation with MaxEPA fish oil (FO) on the plasma concentrations of α-tocopherol, retinol, lipids and lipoproteins in young male subjects were studied. Ten normolipidemic adult male volunteers (25–39 y) supplemented their usual Western diets for 6 wk with 18 g MaxEPA FO per d. Blood samples were collected prior to supplementation, after 6 wk of supplementation, and 10 wk following cessation of the supplement. There was a significant increase (21%) in plasma α-tocopherol concentration after 6 wk of FO supplementation which returned to baseline 10 wk after cessation of the supplements. Plasma retinol increased by 14% and plasma triglyceride (TG) concentration decreased by 28% after 6 wk of supplementation. When FO was taken as a supplement to a typical Western diet significant increases in the concentrations of total cholesterol (TC) (7%), low-density-lipoprotein cholesterol (LDL-C) (10%) and high-density-lipoprotein (HDL-C) (10%) in normolipidemic subjects were observed. Despite animal data indicating an increased need for dietary vitamin E with FO supplementation, in this clinical trial, the FO supplement administed in this study increased plasma α-tocopherol. This increase in due to the 1.35 mg of α-tocopherol added by the manufacturer which appears sufficient to maintain plasma vitamin E levels in the presence of increased PUFA intake, at least over a 6 wk period. Retinyl ester content in eight commercial FO products other than MaxEPA ranged from 2 to 2450 μg/g FO, with a mean of 315 μ/g. The α-tocopherol content in 12 other FO capsules available to consumers for over the counter purchase ranged from 18 to 2241 μg/g FO, with a mean of 1025 μg/g. The effects of ingesting FO supplements with a low content of α-tocopherol on the plasma levels of α-tocopherol needs to be further examined.